Mechanisms of long-term survival of self-reactive helper T cells
| Project/Area Number |
19K07488
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Keio University |
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Principal Investigator |
CHIKUMA Shunsuke 慶應義塾大学, 医学部(信濃町), 准教授 (50437208)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 自己免疫疾患 / ヘルパーＴ細胞 / 慢性炎症 / ヘルパーT細胞 / メモリーT細胞 / Ｔ細胞 / 免疫記憶 |
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| Outline of Research at the Start |
乾癬、リウマチ性関節炎、全身性エリテマトーデス、多発性硬化症といった自己免疫疾患は近年増加の一途をたどり、この病態解明は社会的に緊急かつ重要な課題である。自己免疫疾患の多くは、IL-17産生性ヘルパーT細胞(Th17)によって起こり、寛解と再燃を繰り返す特徴がある。本研究ではTh17依存性自己免疫疾患モデルを用いて、自己反応性Th17が体内において長期間生存し、再活性化して炎症の再燃を起こすメカニズムを探求する。
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| Outline of Final Research Achievements |
IL-17 producing helper T cells (Th17) are suggested in persistent autoimmune diseases. We found that autoreactive Th17 are preferentially maintained and activated in lymphopenic mice and caused severe autoimmune diseases. In addition, mice treated with a cocktail of antibiotics that depleted intestinal microbiota showed almost complete protection from Th17-mediated autoimmunity. Our current data suggest that autoreactive T cells are maintained by intestinal microbiota. Modulating particular intestinal bacteria may provide novel therapy for many autoimmune diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
乾癬、リウマチ性関節炎、全身性エリテマトーデス、多発性硬化症といった慢性の自己免疫疾患は近年増加の一途をたどり、この病態解明は社会的に緊急かつ重要な課題である。マウスを用いて自己反応性Th17が長期生存し、慢性皮膚炎を起こすモデルを確立できた。今後は、このモデルを用いて自己免疫疾患の新規治療法を研究する予定である。また、Th17の生存や活性化に関わる菌およびその抗原などを同定できれば、自己免疫疾患のさらなる理解や治療法につながると考えられる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.2020
Author(s)
Kondo T, Ando M, Nagai N, Tomisato W, Srirat T, Liu B, Mise-Omata S, Ikeda M, Chikuma S, Nishimasu H, Nureki O, Ohmura M, Hayakawa N, Hishiki T, Uchibori R, Ozawa K, Yoshimura A
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Journal Title
Cancer Res
Volume: 80
Issue: 3
Pages: 471-483
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization, and IL-17 expression.2019
Author(s)
Nakatsukasa H, Oda M, Yin J, Chikuma S, Ito M, Koga-Iizuka M, Someya K, Kitagawa Y, Ohkura N, Sakaguchi S, Koya I, Sanosaka T, Kohyama J, Tsukada YI, Yamanaka S, Takamura-Enya T, Lu Q, Yoshimura A
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Journal Title
International immunology
Volume: 31
Issue: 5
Pages: 335-347
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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